We have previously shown that mutations in Cartilage-Derived Morphogenetic Protein-1 (CDMP-1) can cause the clinically distinct disorders, Grebe (OMIM number 200700) and Hunter- Thompson (OMIM#201250) type chondrodysplasia. Both disorders have severe limb shortening, joint dislocations and even complete absence of certain joints. In situ hybridization studies have shown that CDMP-1 is the first gene to be found specifically expressed in presumptive joint interzones. This expression profile could provide a useful basis for designing gene therapeutic approaches to combat degenerative joint disease. With this in mind we began to determine the location of the cartilage and joint-specific regulatory elements using transient transgenic experiments. It became apparent, however, that the cdmp-1 promoter/enhancer region extends at least 100kb upstream, making it difficult to attempt to identify specific elements. Consequently, we have recently initiated an alternative approach, taking advantage of the condensed genome of the puffer fish (fugu rubripes). The puffer fish genome is 10 times smaller than mammalian genomes, but with a similar number of genes, making the regulatory regions and intron sizes much smaller. Cdmp-1 clones have been isolated from a puffer fish genomic library and the exon/intron structure is being characterized. - cartilage, chondrodysplasia, morphogenetic proteins